Left-handed Z-DNA: a DNA structure with biological function?
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Biomedical subjects
E M Lafer
Publications and source records attributed to E M Lafer.
Antibodies to left-handed Z-DNA bind to interband regions of Drosophila polytene chromosomes.
Antibodies which are specific to the Z-DNA conformation have been purified and characterized on the basis of their binding to three different DNA polymers which can form this left-handed helix. These antibodies bind specifically to polytene chromosomes of Drosophila melanogaster as visualized by fluorescent staining. The staining is found in the interband regions and its intensity varies among different interbands in a reproducible manner. This is the first identification of the Z-DNA conformation in material of biological origin.
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Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids.
Hybridomas the produce anti-DNA autoantibodies were prepared from spleen cells of unimmunized MRL/1 mice, a strain that spontaneously develops severe systemic lupus erythematous (SLE). Reactivities of these monoclonal antibodies with a wide range of polynucleotides prompted tests of their reactions with phospholipids which, like polynucleotides, contain diester-linked phosphate groups in their backbones. In competitive radioimmunoassays, cardiolipin, phosphatidic acid, and phosphatidyl glycerol blocked the binding of these hybridoma antibodies to denatured DNA. These phospholipids also specifically inhibited the reaction between a hybridoma antibody and a site-specific anti-idiotypic antibody. The antinuclear reaction of one of these antibodies was specifically inhibited by cardiolipin. This same antibody prolonged the activated partial thromboplastin time in a manner characteristic of a lupus anticoagulant, presumably by binding to phospholipid in the test system. The polyspecific reactivity of a single molecular species of lupus autoantibody suggests that some of the diverse serological abnormalities of SLE may be a result of the binding of certain autoantibodies to a phosphodiester-containing epitope that is present in diverse biological molecules.
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Antibodies specific for left-handed Z-DNA.
We prepared a brominated poly(dG-dC).poly(dG-dC) which forms a stable Z-DNA helix under physiological salt conditions. Rabbits and mice were immunized with brominated and unbrominated poly(dG-dC).poly(dG-dC) complexed with methylated bovine serum albumin. Antibodies specific for Z-DNA were produced. These antibodies were found not only in the sera of animals immunized with the low-salt stabilized Z-DNA [Br-poly(dG-dC).poly(dG-dC)] but also in sera from animals immunized with the unbrominated B-DNA form of the polymer. From this it is inferred that the unbrominated poly(dG-dC).poly(dG-dC) was partially converted to Z-DNA by its combination with the basic protein methylated bovine serum albumin. In addition to specific anti-Z-DNA antibody populations, two other interesting types of antibody populations were found. One of these reacted with both the Z and B forms of poly(dG-dC).poly(dG-dC). This antibody may be converting the polymer from the B-DNA to the Z-DNA form. The other type of antibody was specific for a B form of poly(dG-dC).poly(dG-dC) and did not react at all with the Z form. The antibodies raised to Z-DNA were shown to be highly specific for Z-DNA and did not react with B-DNA, RNA, DNA.RNA hybrids, or a number of other polynucleotides. This specificity for Z-DNA will make possible their use as reagents for determining the presence of Z-DNA in biological systems. Sera of autoimmune lupus mice were also shown to have a considerable amount of naturally occurring anti-Z-DNA antibody activity.
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